Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer

Esophageal Cancer Clinical Trial

Official title:

A Phase III Trial Evaluating the Addition of Cetuximab to Paclitaxel, Cisplatin, and Radiation for Patients With Esophageal Cancer Who Are Treated Without Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00655876
• Other study ID #: RTOG 0436
• Secondary ID: CDR0000538085
• Status: Completed
• Phase: Phase 3
• Start date: June 2008
• Est. completion date: May 20, 2022

Study information

• Verified date: May 2022
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as paclitaxel and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Cetuximab may stop the growth of esophageal cancer by blocking blood flow to the tumor. It is not yet known whether giving paclitaxel and cisplatin together with radiation therapy is more effective with or without cetuximab in treating esophageal cancer. PURPOSE: This randomized phase III trial is comparing how well giving paclitaxel and cisplatin together with radiation therapy works with or without cetuximab in treating patients with locally advanced esophageal cancer.

Description:

OBJECTIVES: Primary - To evaluate whether the addition of cetuximab to chemotherapy comprising paclitaxel, cisplatin, and radiotherapy improves overall survival compared with paclitaxel, cisplatin, and radiotherapy alone in patients with esophageal cancer treated without surgery. Secondary - To evaluate whether the addition of cetuximab to paclitaxel, cisplatin, and radiotherapy improves local control by increasing the clinical complete response and decreasing local recurrence in these patients. - To evaluate adverse events in these patients. - To evaluate endoscopic complete response rates in these patients. - To evaluate if the addition of cetuximab to paclitaxel, cisplatin, and radiotherapy improves the Esophageal Cancer Subscale (ECS) score of the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) quality of life tool. - To evaluate the quality-adjusted survival of each treatment arm using EQ-5D if the primary endpoint supports the primary hypothesis. OUTLINE: This is a multicenter study. Patients are stratified according to histology (adenocarcinoma vs squamous), cancer lesion size (< 5 cm vs ≥ 5 cm), and disease status of celiac nodes (present vs absent). Patients are randomized to 1 of 2 treatment arms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 344
• Est. completion date: May 20, 2022
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 74 Years

Eligibility

Inclusion Criteria:

1. Pathologically (histologic or cytologic) proven diagnosis of primary squamous cell or adenocarcinoma of the esophagus or gastroesophageal junction within 12 weeks prior to registration. Patients with involvement of the gastroesophageal junction with Siewert type I or II tumors (tumors arising from the distal esophagus and involving the esophagogastric junction or tumors starting at the esophagogastric junction and involving the cardia) are eligible.

• 1.1 Disease must be encompassed in a radiotherapy field.
• 1.2 Patients with celiac, perigastric, mediastinal or supraclavicular adenopathy are eligible.
• 1.3 Patients with cervical esophageal carcinoma are eligible.

2. Stage T1N1M0; T2-4, Any N, M0; Any T, Any N, M1a, based upon the following minimum

diagnostic work-up:

• 2.1 History/physical examination within 6 weeks prior to registration
• 2.2 Positron emission tomography (PET)/positron emission tomography-computed tomography (PET-CT) scan (strongly recommended) or chest/abdominal CT within 6 weeks prior to registration
• 2.3 Electrocardiogram (EKG) within 6 weeks of study entry
• 2.4 Endoscopy with biopsy or cytology by fine needle aspiration (FNA) (must be able to document histologic subtype) within 12 weeks of study entry. Patients with T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo bronchoscopy to exclude fistula. (NOTE: Any images from endoscopic procedures up to the time of progression must be kept in the patient's confidential study file.)

3. Zubrod performance status 0-2

4. Age = 18 and = 74 (upper limit was set at 74 in an amendment)

5. Complete blood count (CBC)/differential obtained within 2 weeks prior to registration

on study, with adequate bone marrow function defined as follows:

• 5.1 Absolute neutrophil count (ANC) = 1,500 cells/mm3
• 5.2 Platelets = 100,000 cells/mm3
• 5.3 Hemoglobin = 8.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb =8.0 g/dl is acceptable.)

6. Additional laboratory studies obtained within 2 weeks prior to registration on study

• 6.1 Creatinine = 1.5 mg/dl
• 6.2 Bilirubin = 1.5 x upper limit of normal
• 6.3 Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) = 3 x upper limit of normal
• 6.4 Serum pregnancy test for women of childbearing potential

7. Patient's total intake (oral/enteral) must be = 1500 kCal/day

8. Patient must provide study-specific informed consent prior to study entry

9. Women of childbearing potential and male participants must practice adequate contraception

Exclusion Criteria:

1. Evidence of tracheoesophageal fistula, or invasion into the trachea or major bronchi. Patients with T3-4 proximal thoracic esophageal tumors (15-25 cm) must undergo bronchoscopy to exclude fistula.

2. Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 2 years (For example, carcinoma in situ of the breast, oral cavity, or cervix are all permissible).

3. Prior systemic chemotherapy for esophageal cancer; note that prior chemotherapy for a different cancer is allowable.

4. Prior radiation therapy that would result in overlap of planned radiation therapy fields.

5. Prior therapy that specifically and directly targets the epidermal growth factor receptor (EGFR) pathway.

6. Prior platinum-based and/or paclitaxel-based therapy.

7. Prior allergic reaction to the study drugs involved in this protocol.

8. Prior severe infusion reaction to a monoclonal antibody.

9. Severe, active comorbidity, defined as follows:

• 9.1 Unstable angina and/or congestive heart failure requiring hospitalization within the last 3 months
• 9.2 Transmural myocardial infarction within the last 6 months
• 9.3 Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration
• 9.4 Chronic obstructive pulmonary disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of registration
• 9.5 Acquired immune deficiency syndrome (AIDS) based upon current Centers for Disease Control and Prevention (CDC) definition; note, however, that human immunodeficiency virus (HIV) testing is not required for entry into this protocol. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive. Protocol-specific requirements may also exclude immunocompromised patients.

10. Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic.

11. Women who are nursing.

Related Conditions & MeSH terms

• Esophageal Cancer
• Esophageal Neoplasms

Intervention

Drug:
• cetuximab
Weekly with external beam radiation therapy for a total of six doses. The initial dose of cetuximab is 400 mg/m^2 intravenously administered over 120 minutes on day 1, followed by weekly infusions of 250 mg/m^2 intravenously over 60 minutes on days 8, 15, 22, 29, and 36. The infusion rate of cetuximab must never exceed 5 mL/min.
• cisplatin
Weekly with external beam radiation therapy for a total of six doses. Patients receive 25 mg/m^2 as an intravenous infusion over 30-60 minutes on days 1, 8, 15, 22, 29 and 36.
• paclitaxel
Weekly with external beam radiation therapy for a total of six doses. Patients receive 50 mg/m^2 as an intravenous infusion over 1 hour on days 1, 8, 15, 22, 29 and 36.

Radiation:
• radiation therapy
1.8 Gy daily for 28 days (over 5-6 weeks) for a total dose of 50.4 Gy.

Locations

Country	Name	City	State
Canada	McGill Cancer Centre at McGill University	Montreal	Quebec
Canada	Saint John Regional Hospital	Saint John	New Brunswick
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	New York Oncology Hematology, PC at Albany Regional Cancer Care	Albany	New York
United States	Harrington Cancer Center	Amarillo	Texas
United States	McFarland Clinic, PC	Ames	Iowa
United States	Saint John's Cancer Center at Saint John's Medical Center	Anderson	Indiana
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Mission Hospitals - Memorial Campus	Asheville	North Carolina
United States	Auburn Radiation Oncology	Auburn	California
United States	Rocky Mountain Cancer Centers - Aurora	Aurora	Colorado
United States	Greater Baltimore Medical Center Cancer Center	Baltimore	Maryland
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	St. Agnes Hospital Cancer Center	Baltimore	Maryland
United States	Barberton Citizens Hospital	Barberton	Ohio
United States	Mary Bird Perkins Cancer Center - Baton Rouge	Baton Rouge	Louisiana
United States	UPMC Cancer Center at Beaver Medical Center	Beaver	Pennsylvania
United States	Texas Oncology, PA at Harris Center HEB	Bedford	Texas
United States	MeritCare Bemidji	Bemidji	Minnesota
United States	Billings Clinic - Downtown	Billings	Montana
United States	Lourdes Regional Cancer Center	Binghamton	New York
United States	Bloomington Hospital Regional Cancer Institute	Bloomington	Indiana
United States	Saint Alphonsus Cancer Care Center at Saint Alphonsus Regional Medical Center	Boise	Idaho
United States	Alamance Cancer Center at Alamance Regional Medical Center	Burlington	North Carolina
United States	Radiation Oncology Centers - Cameron Park	Cameron Park	California
United States	Aultman Cancer Center at Aultman Hospital	Canton	Ohio
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Mercy Cancer Center at Mercy San Juan Medical Center	Carmichael	California
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Chicago Cancer Research Center	Chicago	Illinois
United States	Enloe Cancer Center at Enloe Medical Center	Chico	California
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	UPMC Cancer Center at Jefferson Regional Medical Center	Clairton	Pennsylvania
United States	Case Comprehensive Cancer Center	Cleveland	Ohio
United States	MetroHealth Cancer Care Center at MetroHealth Medical Center	Cleveland	Ohio
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Payson Center for Cancer Care at Concord Hospital	Concord	New Hampshire
United States	Mercy and Unity Cancer Center at Mercy Hospital	Coon Rapids	Minnesota
United States	Texas Oncology, PA at Texas Cancer Center - Denton South	Denton	Texas
United States	Porter Adventist Hospital	Denver	Colorado
United States	John Stoddard Cancer Center at Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Cancer Center at Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Josephine Ford Cancer Center at Henry Ford Hospital	Detroit	Michigan
United States	Seacoast Cancer Center at Wentworth - Douglass Hospital	Dover	New Hampshire
United States	Delaware County Regional Cancer Center at Delaware County Memorial Hospital	Drexel Hill	Pennsylvania
United States	Regional Cancer Center - Erie	Erie	Pennsylvania
United States	Willamette Valley Cancer Center - Eugene	Eugene	Oregon
United States	Center for Cancer Care at Exeter Hospital	Exeter	New Hampshire
United States	Hudner Oncology Center at Saint Anne's Hospital - Fall River	Fall River	Massachusetts
United States	CCOP - MeritCare Hospital	Fargo	North Dakota
United States	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Parkview Regional Cancer Center at Parkview Health	Fort Wayne	Indiana
United States	Radiation Oncology Associates Southwest	Fort Wayne	Indiana
United States	Klabzuba Cancer Center at Harris Methodist Fort Worth Hospital	Fort Worth	Texas
United States	California Cancer Center - Woodward Park Office	Fresno	California
United States	Saint Agnes Cancer Center at Saint Agnes Medical Center	Fresno	California
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	Adams Cancer Center	Gettysburg	Pennsylvania
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	St. Mary's Hospital Medical Center - Green Bay	Green Bay	Wisconsin
United States	St. Vincent Hospital Regional Cancer Center	Green Bay	Wisconsin
United States	UPMC Cancer Center - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Cancer Centers of the Carolinas - Faris Road	Greenville	South Carolina
United States	CCOP - Greenville	Greenville	South Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Cancer Research Center of Hawaii	Honolulu	Hawaii
United States	Hawaii Medical Center - East	Honolulu	Hawaii
United States	Queen's Cancer Institute at Queen's Medical Center	Honolulu	Hawaii
United States	Memorial Hermann Hospital - Memorial City	Houston	Texas
United States	Central Indiana Cancer Centers - East	Indianapolis	Indiana
United States	Methodist Cancer Center at Methodist Hospital	Indianapolis	Indiana
United States	University of Mississippi Cancer Clinic	Jackson	Mississippi
United States	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida
United States	West Michigan Cancer Center	Kalamazoo	Michigan
United States	Kingsbury Center for Cancer Care at Cheshire Medical Center	Keene	New Hampshire
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Thompson Cancer Survival Center	Knoxville	Tennessee
United States	Center for Cancer Care and Research at Watson Clinic, LLP	Lakeland	Florida
United States	CCOP - Nevada Cancer Research Foundation	Las Vegas	Nevada
United States	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Monmouth Medical Center	Long Branch	New Jersey
United States	Longview Cancer Center	Longview	Texas
United States	James Graham Brown Cancer Center at University of Louisville	Louisville	Kentucky
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Elliot Regional Cancer Center at Elliot Hospital	Manchester	New Hampshire
United States	Minnesota Oncology - Maplewood	Maplewood	Minnesota
United States	Bay Area Cancer Care Center at Bay Area Medical Center	Marinette	Wisconsin
United States	Fox Chase Virtua Health Cancer Program at Virtua Memorial Hospital Marlton	Marlton	New Jersey
United States	Mercy Cancer Center at Mercy Medical Center - North Iowa	Mason City	Iowa
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Lake/University Ireland Cancer Center	Mentor	Ohio
United States	Baptist-South Miami Regional Cancer Program	Miami	Florida
United States	CCOP - Mount Sinai Medical Center	Miami Beach	Florida
United States	Southwest General Health Center	Middleburg Heights	Ohio
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Memorial Medical Center	Modesto	California
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	Jon and Karen Huntsman Cancer Center at Intermountain Medical Center	Murray	Utah
United States	George Bray Cancer Center at the Hospital of Central Connecticut - New Britain Campus	New Britain	Connecticut
United States	Beth Israel Medical Center - Petrie Division	New York	New York
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	St. Luke's - Roosevelt Hospital Center - St.Luke's Division	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	William W. Backus Hospital	Norwich	Connecticut
United States	Regional Cancer Center at Oconomowoc Memorial Hospital	Oconomowoc	Wisconsin
United States	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma
United States	Lakeside Hospital	Omaha	Nebraska
United States	Methodist Estabrook Cancer Center	Omaha	Nebraska
United States	UHHS Chagrin Highlands Medical Center	Orange Village	Ohio
United States	M.D. Anderson Cancer Center at Orlando	Orlando	Florida
United States	Advocate Lutheran General Cancer Care Center	Park Ridge	Illinois
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Frankford Hospital Cancer Center - Torresdale Campus	Philadelphia	Pennsylvania
United States	UPMC - Shadyside	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC Passavant	Pittsburgh	Pennsylvania
United States	UPMC Cancer Center at UPMC St. Margaret	Pittsburgh	Pennsylvania
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Northmain Radiation Oncology	Providence	Rhode Island
United States	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	Robinson Radiation Oncology	Ravenna	Ohio
United States	McGlinn Family Regional Cancer Center at Reading Hospital and Medical Center	Reading	Pennsylvania
United States	Swedish-American Regional Cancer Center	Rockford	Illinois
United States	Radiation Oncology Center - Roseville	Roseville	California
United States	Mercy General Hospital	Sacramento	California
United States	Radiological Associates of Sacramento Medical Group, Incorporated	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Dixie Regional Medical Center - East Campus	Saint George	Utah
United States	David C. Pratt Cancer Center at St. John's Mercy	Saint Louis	Missouri
United States	Missouri Baptist Cancer Center	Saint Louis	Missouri
United States	Saint Louis University Cancer Center	Saint Louis	Missouri
United States	Regions Hospital Cancer Care Center	Saint Paul	Minnesota
United States	United Hospital	Saint Paul	Minnesota
United States	Huntsman Cancer Institute at University of Utah	Salt Lake City	Utah
United States	Utah Cancer Specialists at UCS Cancer Center	Salt Lake City	Utah
United States	Cancer Care Centers of South Texas - Northeast	San Antonio	Texas
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Cancer Centers of the Carolinas - Seneca	Seneca	South Carolina
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Texas Oncology, PA at Texas Cancer Center - Sherman	Sherman	Texas
United States	Siouxland Hematology-Oncology Associates, LLP	Sioux City	Iowa
United States	Sanford Cancer Center at Sanford USD Medical Center	Sioux Falls	South Dakota
United States	Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York
United States	Memorial Hospital of South Bend	South Bend	Indiana
United States	Frederick R. and Betty M. Smith Cancer Treatment Center	Sparta	New Jersey
United States	Cancer Centers of the Carolinas - Spartanburg	Spartanburg	South Carolina
United States	CCOP - Upstate Carolina	Spartanburg	South Carolina
United States	Gibbs Regional Cancer Center at Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	Cancer Institute at St. John's Hospital	Springfield	Illinois
United States	Door County Cancer Center at Door County Memorial Hospital	Sturgeon Bay	Wisconsin
United States	Texas Oncology, PA at Texas Oncology Cancer Center Sugar Land	Sugar Land	Texas
United States	J. Phillip Citta Regional Cancer Center at Community Medical Center	Toms River	New Jersey
United States	Arizona Oncology - Tucson	Tucson	Arizona
United States	Natalie Warren Bryant Cancer Center at St. Francis Hospital	Tulsa	Oklahoma
United States	Tyler Cancer Center	Tyler	Texas
United States	Solano Radiation Oncology Center	Vacaville	California
United States	Sutter Solano Medical Center	Vallejo	California
United States	Northwest Cancer Specialists at Vancouver Cancer Center	Vancouver	Washington
United States	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey
United States	Waukesha Memorial Hospital Regional Cancer Center	Waukesha	Wisconsin
United States	University of Wisconcin Cancer Center at Aspirus Wausau Hospital	Wausau	Wisconsin
United States	UHHS Westlake Medical Center	Westlake	Ohio
United States	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	Texas Oncology, PA - Wichita Falls	Wichita Falls	Texas
United States	York Cancer Center at Apple Hill Medical Center	York	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI), NRG Oncology

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (1)

Suntharalingam M, Winter K, Ilson D, Dicker AP, Kachnic L, Konski A, Chakravarthy AB, Anker CJ, Thakrar H, Horiba N, Dubey A, Greenberger JS, Raben A, Giguere J, Roof K, Videtic G, Pollock J, Safran H, Crane CH. Effect of the Addition of Cetuximab to Pacl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (24-month Rate Reported)	Survival time is defined as time from randomization to date of death from any cause and is estimated by the Kaplan-Meier method. Patients last known to be alive are censored at the date of last contact. This analysis was planned to occur after at least 281 deaths have been observed, unless an early stopping rule was satisfied.	From randomization to last follow-up. Analysis was planned to occur after at least 281 deaths had been observed. Maximum follow-up at time of analysis was 74.5 months.
Secondary	Local Failure (24-month Rate Reported)	Local failure (LF) was defined as residual cancer on posttreatment biopsy findings or biopsy-proven recurrent primary disease and local failure time was measured from randomization to failure or last follow-up. Nonprotocol surgery to the primary site with gross residual disease was considered a LF as of the surgery date. Patients with no viable disease or microscopic residual disease at nonprotocol surgery were censored for LF as of the surgery date. Local failure was estimated by the cumulative incidence method with death considered a competing risk.	From randomization to last follow-up. Analysis was planned to occur after at least 281 deaths had been observed. Maximum follow-up at time of analysis was 74.5 months.
Secondary	Percentage of Patients With Acute Grade 4 or 5 Non-hematologic Treatment-related Adverse Events	Adverse events (AE) are graded using CTCAE v3.0. Grade refers to the severity of the AE. The CTCAE v3.0 assigns Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild AE, Grade 2 Moderate AE, Grade 3 Severe AE, Grade 4 Life-threatening or disabling AE, Grade 5 Death related to AE	From start of treatment to 90 days from end of treatment
Secondary	Endoscopic Complete Response Rate	All patients were to undergo a repeat endoscopy (EUS) 6-8 weeks after the completion of chemoradiation. At the time of EUS a visual inspection of the site of the original primary disease would be documented. Those patients found to be free of disease were NOT required to undergo repeat biopsy. These patients would be scored as clinical complete responses (cCR). Patients deemed to have residual disease or suspicion of residual disease would undergo a biopsy in order to pathologically confirm findings. Any patient with pathologically confirmed residual disease would be scored as a local failure. Patients who were pathologically proven to have no evidence of disease would be scored as cCRs.	From randomization to 6-8 weeks after completion of chemoradiation (11-14 weeks)
Secondary	Percentage of Patients With Improvement in the Functional Assessment of Cancer Therapy - Esophagus (FACT-E) Esophageal Cancer Subscale (ECS) Subscale After Treatment	The ECS is a 17-item self-report instrument designed to measure multidimensional quality of life in patients with esophagus cancer. It is to be administered with the Functional Assessment of Cancer Therapy - General (FACT-G). There are 5 responses options, with 0=Not a lot and 4=Very much. All items are added together to obtain a total score which ranges from 0-68. Certain items must be reversed before it is added by subtracting the response from 4. It requires at least 50% of the items to be completed while the overall response rate of the FACT-E including the FACT-G must be greater than 80%. If items are missing, the subscale scores can be prorated. A higher score indicated better QOL. Improvement in FACT-E score is defined as an increase from baseline score of at least 5 points.	Baseline, 6-8 weeks after completion of chemoradiation , 1 year and 2 years from treatment start.
Secondary	Quality-adjusted Survival (Using EQ-5D), Only if Primary Hypothesis is Supported		Baseline, 6-8 weeks after completion of chemoradiation, 1 year and 2 years from treatment start.